Functional aspects of the somatostatinergic system in the retina and the potential therapeutic role of somatostatin in retinal disease

Abstract

The somatostatinergic system of the retina has been investigated in a variety of studies. A considerable amount of experimental evidence is available concerning the patterns of expression of somatostatin (SRIF) and its receptors in vertebrate retinas. However the functional roles of this peptidergic system in retinal physiology are far from being elucidated. Nonetheless, data have been provided concerning the regulatory action of SRIF on the excitability of different retinal cell types and on the modulation of ion channels in different vertebrate retinas. The present review is focused on recent and unpublished investigations of the mouse retina relative to the involvement of specific SRIF receptors in the regulation of ion channels and transmitter release, the transduction pathways coupled to SRIF receptors, and the mechanisms regulating the expression of SRIF and its receptors as derived from studies in transgenic animal models. In these models, altered expression levels of SRIF or of specific SRIF receptors have also been found to affect the morphology of retinal cell types (namely the rod bipolar cells) and to result in functional alterations at the level of both ion channel regulation and transmitter release. These new pieces of evidence constitute an important step forward in the understanding of the functional actions of the retinal somatostatinergic system, although our current knowledge is far from being exhaustive. The ultimate goal of understanding SRIF functional actions in the retina is concerned with the possibility of using SRIF or its analogs as therapeutic agents to cure retinal diseases. Indeed, encouraging results are being obtained in clinical investigations focused on the use of SRIF analogs to treat diabetic retinopathy, a retinal disease with high social impact and originating as a complication of diabetes. The closing part of the present paper examines the evidence supporting SRIF as a promising therapeutic agent in this disease.